20 min listen
Effects of six pyrimidine analogs on the growth of Tetrahymena thermophila and their implications in pyrimidine metabolism
Effects of six pyrimidine analogs on the growth of Tetrahymena thermophila and their implications in pyrimidine metabolism
ratings:
Length:
20 minutes
Released:
Mar 31, 2023
Format:
Podcast episode
Description
Link to bioRxiv paper:
http://biorxiv.org/cgi/content/short/2023.03.29.534814v1?rss=1
Authors: Chang, W.-J., Harpel, Z., Circelli, J., Chen, R., Chang, I., Rivera, J., Wu, S., Wei, Z.
Abstract:
Tetrahymena are ciliated protists that have been used to study the effects of toxic chemicals, including anticancer drugs. In this study, we tested the inhibitory effects of six pyrimidine analogs (5-fluorouracil, floxuridine, 5-deoxy-5-fluorouridine, 5-fluorouridine, gemcitabine, cytarabine) on wild-type CU428 and conditional mutant NP1 Tetrahymena thermophila at room temperature and the restrictive temperature (37{degrees}C) where NP1 does not form the oral apparatus. We found that cytarabine was the only tested analog that did not inhibit growth, and phagocytosis was not required for pyrimidine analog entry. IC50 values did not significantly differ between strains for the same analog at either temperature. To investigate the mechanism of inhibition, we used two pyrimidine bases (uracil and thymine) and three nucleosides (uridine, thymidine, 5-methyluridine) to help determine whether the inhibitory effects from analogs were reversible. We found that the inhibitory effects from 5-fluorouracil could be reversed by uracil and thymine, from floxuridine could be reversed by thymidine, and from 5-deoxy-5-fluorouridine could be reversed by uracil. None of the tested nucleobases or nucleosides could reverse the inhibitory effects of gemcitabine or 5-fluorouridine. Our results suggest that the five pyrimidine analogs act on different sites to inhibit T. thermophila growth and that nucleobases and nucleosides are metabolized differently.
Copy rights belong to original authors. Visit the link for more info
Podcast created by Paper Player, LLC
http://biorxiv.org/cgi/content/short/2023.03.29.534814v1?rss=1
Authors: Chang, W.-J., Harpel, Z., Circelli, J., Chen, R., Chang, I., Rivera, J., Wu, S., Wei, Z.
Abstract:
Tetrahymena are ciliated protists that have been used to study the effects of toxic chemicals, including anticancer drugs. In this study, we tested the inhibitory effects of six pyrimidine analogs (5-fluorouracil, floxuridine, 5-deoxy-5-fluorouridine, 5-fluorouridine, gemcitabine, cytarabine) on wild-type CU428 and conditional mutant NP1 Tetrahymena thermophila at room temperature and the restrictive temperature (37{degrees}C) where NP1 does not form the oral apparatus. We found that cytarabine was the only tested analog that did not inhibit growth, and phagocytosis was not required for pyrimidine analog entry. IC50 values did not significantly differ between strains for the same analog at either temperature. To investigate the mechanism of inhibition, we used two pyrimidine bases (uracil and thymine) and three nucleosides (uridine, thymidine, 5-methyluridine) to help determine whether the inhibitory effects from analogs were reversible. We found that the inhibitory effects from 5-fluorouracil could be reversed by uracil and thymine, from floxuridine could be reversed by thymidine, and from 5-deoxy-5-fluorouridine could be reversed by uracil. None of the tested nucleobases or nucleosides could reverse the inhibitory effects of gemcitabine or 5-fluorouridine. Our results suggest that the five pyrimidine analogs act on different sites to inhibit T. thermophila growth and that nucleobases and nucleosides are metabolized differently.
Copy rights belong to original authors. Visit the link for more info
Podcast created by Paper Player, LLC
Released:
Mar 31, 2023
Format:
Podcast episode
Titles in the series (100)
A genome-wide CRISPR interference screen using an engineered trafficking biosensor reveals a role for RME-8 in opioid receptor regulation by PaperPlayer biorxiv cell biology